tbuckley/cabot-search huggingface dataset:
Changes in life expectancy and disease burden in Norway, 1990–2019: an analysis of the Global Burden of Disease Study 2019
Authors: Benjamin Clarsen, Magne Nylenna, Søren Toksvig Klitkou, Stein Emil Vollset, Carl Michael Baravelli, Anette Kocbach Bølling, Gunn Marit Aasvang, Gerhard Sulo, Mohsen Naghavi, Maja Pasovic, Muhammad Asaduzzaman, Tone Bjørge, Anne Elise Eggen, Terje Andreas Eikemo, Christian Lycke Ellingsen, Øystein Ariansen Haaland, Alemayehu Hailu, Shoaib Hassan, Simon I Hay, Petur B Juliusson, Adnan Kisa, Sezer Kisa, Johan Månsson, Teferi Mekonnen, Christopher J L Murray, Ole F Norheim, Trygve Ottersen, Dominic Sagoe, Kam Sripada, Andrea Sylvia Winkler, Ann Kristin Skrindo Knudsen
Journal: The Lancet Public Health (2022)

Geographical differences in health outcomes are reported in many countries. Norway has led an active policy aiming for regional balance since the 1970s. Using data from the Global Burden of Disease Study (GBD) 2019, we examined regional differences in development and current state of health across Norwegian counties.Data for life expectancy, healthy life expectancy (HALE), years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) in Norway and its 11 counties from 1990 to 2019 were extracted from GBD 2019. County-specific contributors to changes in life expectancy were compared. Inequality in disease burden was examined by use of the Gini coefficient.Life expectancy and HALE improved in all Norwegian counties from 1990 to 2019. Improvements in life expectancy and HALE were greatest in the two counties with the lowest values in 1990: Oslo, in which life expectancy and HALE increased from 71·9 years (95% uncertainty interval 71·4-72·4) and 63·0 years (60·5-65·4) in 1990 to 81·3 years (80·0-82·7) and 70·6 years (67·4-73·6) in 2019, respectively; and Troms og Finnmark, in which life expectancy and HALE increased from 71·9 years (71·5-72·4) and 63·5 years (60·9-65·6) in 1990 to 80·3 years (79·4-81·2) and 70·0 years (66·8-72·2) in 2019, respectively. Increased life expectancy was mainly due to reductions in cardiovascular disease, neoplasms, and respiratory infections. No significant differences between the national YLD or DALY rates and the corresponding age-standardised rates were reported in any of the counties in 2019; however, Troms og Finnmark had a higher age-standardised YLL rate than the national rate (8394 per 100 000 [95% UI 7801-8944] vs 7536 per 100 000 [7391-7691]). Low inequality between counties was shown for life expectancy, HALE, all level-1 causes of DALYs, and exposure to level-1 risk factors.Over the past 30 years, Norway has reduced inequality in disease burden between counties. However, inequalities still exist at a within-county level and along other sociodemographic gradients. Because of insufficient Norwegian primary data, there remains substantial uncertainty associated with regional estimates for non-fatal disease burden and exposure to risk factors.Bill & Melinda Gates Foundation, Research Council of Norway, and Norwegian Institute of Public Health.
Physioxia-induced downregulation of <i>Tet2</i> in hematopoietic stem cells contributes to enhanced self-renewal
Authors: Arafat Aljoufi, Chi Zhang, James Ropa, Wennan Chang, Lakshmi Reddy Palam, Scott Cooper, Baskar Ramdas, Maegan L. Capitano, Hal E. Broxmeyer, Reuben Kapur
Journal: Blood (2022)

Abstract Hematopoietic stem cells (HSCs) manifest impaired recovery and self-renewal with a concomitant increase in differentiation when exposed to ambient air as opposed to physioxia. Mechanism(s) behind this distinction are poorly understood but have the potential to improve stem cell transplantation. Single-cell RNA sequencing of HSCs in physioxia revealed upregulation of HSC self-renewal genes and downregulation of genes involved in inflammatory pathways and HSC differentiation. HSCs under physioxia also exhibited downregulation of the epigenetic modifier Tet2. Tet2 is α-ketoglutarate, iron- and oxygen-dependent dioxygenase that converts 5-methylcytosine to 5-hydroxymethylcytosine, thereby promoting active transcription. We evaluated whether loss of Tet2 affects the number and function of HSCs and hematopoietic progenitor cells (HPCs) under physioxia and ambient air. In contrast to wild-type HSCs (WT HSCs), a complete nonresponsiveness of Tet2−/− HSCs and HPCs to changes in oxygen tension was observed. Unlike WT HSCs, Tet2−/− HSCs and HPCs exhibited similar numbers and function in either physioxia or ambient air. The lack of response to changes in oxygen tension in Tet2−/− HSCs was associated with similar changes in self-renewal and quiescence genes among WT HSC-physioxia, Tet2−/− HSC-physioxia and Tet2−/− HSC-air. We define a novel molecular program involving Tet2 in regulating HSCs under physioxia.
Household Food Insecurity and Fear of Hypoglycemia in Adolescents and Young Adults With Diabetes and Parents of Youth With Diabetes
Authors: Lauren A. Reid, Siyu Zheng, Jason A. Mendoza, Beth A. Reboussin, Alissa J. Roberts, Katherine A. Sauder, Jean M. Lawrence, Elizabeth Jensen, Leora Henkin, Kate Flory, Lisa M. Knight, Catherine Pihoker, Lawrence M. Dolan, Elaine M. Apperson, Angela D. Liese
Journal: Diabetes Care (2022)

OBJECTIVE To evaluate the relation between household food insecurity (HFI) and fear of hypoglycemia among young adults with type 1 and type 2 diabetes and adolescents with type 1 diabetes and their parents. RESEARCH DESIGN AND METHODS We analyzed cross-sectional data of 1,676 young adults with youth-onset diabetes (84% type 1, 16% type 2) and 568 adolescents (&amp;lt;18 years old; mean age 15.1 years) with type 1 diabetes from the SEARCH for Diabetes in Youth study. Adult participants and parents of adolescent participants completed the U.S. Household Food Security Survey Module. Adults, adolescents, and parents of adolescents completed the Hypoglycemia Fear Survey, where answers range from 1 to 4. The outcomes were mean score for fear of hypoglycemia and the behavior and worry subscale scores. Linear regression models identified associations between HFI and fear of hypoglycemia scores. RESULTS Adults with type 1 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.22 units higher for behavior, 0.55 units for worry, 0.40 units for total; all P &amp;lt; 0.0001) than those without HFI. No differences by HFI status were found for adolescents with type 1 diabetes. Parents of adolescents reporting HFI had a 0.18 unit higher worry score than those not reporting HFI (P &amp;lt; 0.05). Adults with type 2 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.19 units higher for behavior, 0.35 units for worry, 0.28 units for total; all P &amp;lt; 0.05) than those in food secure households. CONCLUSIONS Screening for HFI and fear of hypoglycemia among people with diabetes can help providers tailor diabetes education for those who have HFI and therefore fear hypoglycemia.
Risk factors and communities disproportionately affected by cervical cancer in the Russian Federation: A national population-based study
Authors: Anastasiya Muntyanu, Vladimir Nechaev, Elena Pastukhova, James Logan, Elham Rahme, Elena Netchiporouk, Andrei Zubarev, Ivan V. Litvinov
Journal: The Lancet Regional Health - Europe (2022)

Cervical cancer is one of the leading causes of cancer in women of childbearing age worldwide. A substantial fraction of cervical cancer is associated with Human Papilloma Virus (HPV) infection and is preventable through vaccination and screening. The aim of the study is to describe geographic and epidemiologic trends in incidence and mortality of cervical cancer in Russia during 2007-2018.Publicly accessible data from the P.A. Herzen Moscow Oncology Research Institute and the Ministry of Health of Russian Federation for 2007-2018 was used for this study. Cervical cancer incidence and mortality rates were analyzed using descriptive statistics and results were mapped to determine the geographic distribution. Potential contributing risk factors in the population were studied using univariate and multivariate Poisson regression analyses.A total of 187,013 patients were diagnosed with cervical cancer in Russia between 2007 and 2018. The average age-standardized incidence (ASIR) and mortality rates (ASMR) were 15.70/100,000 and 5.76/100,000 females, respectively, with a 27% increase in the incidence observed between 2007 and 2018. The highest ASIR was observed in the Far Eastern Federal District and the lowest in the Central Federal District. Multivariate model for cervical cancer ASIR showed that daily smoking (p = 0·0003) and syphilis (p = 0.003) were significantly associated with cervical cancer incidence.The incidence of cervical cancer in Russia is rising at a significant pace. This trend can in part be attributed to a lack of nationwide cervical cancer screening . The presented results are valuable for informing public health policy on HPV vaccinations, smoking prevention and cervical cancer screening as urgent interventions are needed to combat a troubling trend.This work was supported by the Cancer Research Society (CRS)-Canadian Institutes for Health Research (CIHR) Partnership Grant #25343 to Dr. Litvinov. Canadian Dermatology Foundation research grant to Dr. Litvinov, and by the Fonds de la recherche du Québec - Santé to Dr. Sasseville (#22648) and to Dr. Litvinov (#34753 and #36769). This research was further supported by the CIHR Catalyst Grant #428712 to Dr. Litvinov.
TGF-β1–induced endothelial-mesenchymal transition: a potential contributor to fibrotic remodeling in atrial fibrillation?
Authors: Arnela Saljic, Eleonora Grandi, Dobromir Dobrev
Journal: Journal of Clinical Investigation (2022)

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide, with an unmet therapeutic need. Fibrotic remodeling, in which collagen-producing atrial fibroblasts play a crucial role, substantially contributes to arrhythmia promotion and progression. In this issue of the JCI, Lai, Tsai, and co-authors reveal that TGF-β1 promoted endothelial-mesenchymal transition during AF and put forward the notion that, in the adult heart, atrial fibroblasts can originate from different cellular sources. These important findings extend our understanding of the origin, biology, and function of fibroblasts and offer possibilities for therapeutic targeting of fibrosis in AF.
Intratumoral immunotherapy using a TLR2/3 agonist, L-pampo, induces robust antitumor immune responses and enhances immune checkpoint blockade
Authors: Won Suk Lee, Dong Sung Kim, Jeong Hun Kim, Yoonki Heo, Hannah Yang, Eun-Jin Go, Jin Hyoung Kim, Seung Joon Lee, Byung Cheol Ahn, Jung Sun Yum, Hong Jae Chon, Chan Kim
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Toll-like receptors (TLRs) are critical innate immune sensors that elicit antitumor immune responses in cancer immunotherapy. Although a few TLR agonists have been approved for the treatment of patients with early-stage superficial cancers, their therapeutic efficacy is limited in patient with advanced invasive cancers. Here, we identified the therapeutic role of a TLR2/3 agonist, L-pampo (LP), which promotes antitumor immunity and enhances the immune checkpoint blockade. Methods We generated LP by combining a TLR2 agonist, Pam3CSK4, with a TLR3 agonist, Poly (I:C). Immune responses to stimulation with various TLR agonists were compared. Tumor-bearing mice were intratumorally treated with LP, and their tumor sizes were measured. The antitumor effects of LP treatment were determined using flow cytometry, multiplexed imaging, and NanoString nCounter immune profiling. The immunotherapeutic potential of LP in combination with α-programmed cell death protein-1 (PD-1) or α-cytotoxic T-lymphocytes-associated protein 4 (CTLA-4) was evaluated in syngeneic MC38 colon cancer and B16F10 melanoma. Results The LP treatment induced a potent activation of T helper 1 (Th1) and 2 (Th2)-mediated immunity, tumor cell apoptosis, and immunogenic tumor cell death. Intratumoral LP treatment effectively inhibited tumor progression by activating tumor-specific T cell immunity. LP-induced immune responses were mediated by CD8 + T cells and interferon-γ, but not by CD4 + T cells and CD25 + T cells. LP simultaneously activated TLR2 and TLR3 signaling, thereby extensively changing the immune-related gene signatures within the tumor microenvironment (TME). Moreover, intratumoral LP treatment led to systemic abscopal antitumor effects in non-injected distant tumors. Notably, LP treatment combined with ɑPD-1 and ɑCTLA-4 further enhanced the efficacy of monotherapy, resulting in complete tumor regression and prolonged overall survival. Furthermore, LP-based combination immunotherapy elicited durable antitumor immunity with tumor-specific immune memory in colon cancer and melanoma. Conclusions Our study demonstrated that intratumoral LP treatment improves the innate and adaptive antitumor immunity within the TME and enhances the efficacy of αPD-1 and αCTLA-4 immune checkpoint blockade.
Tracheobronchial Smooth Muscle Atrophy and Separation
Authors: Prince Ntiamoah, Adam Fawaz, Atul C. Mehta, Thomas R. Gildea
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Tracheobronchial Smooth Muscle Atrophy and Separation." American Journal of Respiratory and Critical Care Medicine, 206(7), p. e73
ID2 and HIF-1α collaborate to protect quiescent hematopoietic stem cells from activation, differentiation, and exhaustion
Authors: Brad L. Jakubison, Tanmoy Sarkar, Kristbjorn O. Gudmundsson, Shweta Singh, Lei Sun, Holly M. Morris, Kimberly D. Klarmann, Jonathan R. Keller
Journal: Journal of Clinical Investigation (2022)

Defining mechanism(s) that maintain tissue stem quiescence is important for improving tissue regeneration, cell therapies, aging, and cancer. We report here that genetic ablation of Id2 in adult hematopoietic stem cells (HSCs) promotes increased HSC activation and differentiation, which results in HSC exhaustion and bone marrow failure over time. Id2Δ/Δ HSCs showed increased cycling, ROS production, mitochondrial activation, ATP production, and DNA damage compared with Id2+/+ HSCs, supporting the conclusion that Id2Δ/Δ HSCs are less quiescent. Mechanistically, HIF-1α expression was decreased in Id2Δ/Δ HSCs, and stabilization of HIF-1α in Id2Δ/Δ HSCs restored HSC quiescence and rescued HSC exhaustion. Inhibitor of DNA binding 2 (ID2) promoted HIF-1α expression by binding to the von Hippel-Lindau (VHL) protein and interfering with proteasomal degradation of HIF-1α. HIF-1α promoted Id2 expression and enforced a positive feedback loop between ID2 and HIF-1α to maintain HSC quiescence. Thus, sustained ID2 expression could protect HSCs during stress and improve HSC expansion for gene editing and cell therapies.
Oncolytic DNX-2401 Virus for Pediatric Diffuse Intrinsic Pontine Glioma
Authors: Jaime Gállego Pérez-Larraya, Marc Garcia-Moure, Sara Labiano, Ana Patiño-García, Jessica Dobbs, Marisol Gonzalez-Huarriz, Marta Zalacain, Lucia Marrodan, Naiara Martinez-Velez, Montserrat Puigdelloses, Virginia Laspidea, Itziar Astigarraga, Blanca Lopez-Ibor, Ofelia Cruz, Miren Oscoz Lizarbe, Sandra Hervas-Stubbs, Gorka Alkorta-Aranburu, Ibon Tamayo, Beatriz Tavira, Ruben Hernandez-Alcoceba, Chris Jones, Gitanjali Dharmadhikari, Cristian Ruiz-Moreno, Henk Stunnenberg, Esther Hulleman, Jasper van der Lugt, Miguel Á. Idoate, Ricardo Diez-Valle, Inés Esparragosa Vázquez, Maria Villalba, Carlos de Andrea, Jorge M. Núñez-Córdoba, Brett Ewald, Joan Robbins, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F. Lang, Sonia Tejada, Marta M. Alonso
Journal: New England Journal of Medicine (2022)

Pediatric patients with diffuse intrinsic pontine glioma (DIPG) have a poor prognosis, with a median survival of less than 1 year. Oncolytic viral therapy has been evaluated in patients with pediatric gliomas elsewhere in the brain, but data regarding oncolytic viral therapy in patients with DIPG are lacking.
Ann Robinson’s research reviews—30 June 2022
Authors: Ann Robinson
Journal: BMJ (2022)

Spare the tonsils?I'm from a generation whose tonsils and adenoids were whipped out at the first hint of snuffles or sore throats.In the UK, the pendulum has swung towards a more rational approach, which means tonsillectomy and adenoidectomy have become relatively rare procedures on the NHS with very specific and limited indications.This large retrospective cohort study of over half a million children (median age 7 years) in five US states reminds us that no operation is ever without risk.
Using Magnetic Resonance Liver Non-Contrast Perfusion in Patients with Diffuse Liver Diseases
Authors: A. A. Telesh, T. G. Morozova
Journal: Radiology - Practice (2022)

The aim of this work is to evaluate possibilities of MR liver non-contrast perfusion in patients with diffuse liver diseases (DLD). Laboratory data, results of ultrasound examination with doppler ultrasonography of liver vessels, results of MRI with non-contrast MR perfusion (ASL-perfusion) of the liver was estimated in a group of patients with DLD. Potentials of assessment of ASL liver perfusion for clinical form prediction are described in the article. Potentials of using the assessment of ASL liver perfusion for information about a liver blood flow type and process activity indicators by blood chemistry are also described. It was established, that ASL MR of the liver is recommended to use in patients with diffuse liver diseases who admitted to a hospital, then in 1 month (in case of hypo/hyperperfusion) or in 6 months (in case of normal perfusion).
Bioinspired Vascular Stents with Microfluidic Electrospun Multilayer Coatings for Preventing In‐Stent Restenosis
Authors: Yi Cheng, Xiaoxuan Zhang, Rui Liu, Yazhou Li, Jiaqi Zeng, Min Zhou, Yuanjin Zhao
Journal: Advanced Healthcare Materials (2022)

Abstract In‐stent restenosis (ISR) is seriously affecting the long‐term prognosis of vascular interventional therapy and leading to enormous medical burdens. Great efforts have been devoted to developing functional vascular stents with desired features and properties for effective ISR prevention. Here, a multifunctional bionic vascular stent with designed coatings prepared using microfluidic electrospinning technology is presented. Such stents are composed of biocompatible, drug‐loaded methylacrylated gelatin‐polyethylene glycol diacrylate (GelMA‐PEGDA) and polycaprolactone composite nanofibers on 316L stainless steel stents by an easy‐to‐operate step‐by‐step spraying method. Benefitting from the addition of polydopamine during the fabrications, the drug‐loaded composite nanofibers can adhere well to both the stent and the vascular wall. Furthermore, as the inner fibrous layer of the stent contacting the lumen is equipped with heparin‐vascular endothelial growth factor (Hep‐VEGF), it plays an anticoagulation role and promotes the growth of endothelial cells; while the outer layer contacts the vascular wall and releases rapamycin slowly, which can restrain smooth muscle proliferation. By implanting this into the rabbit carotid artery, the multi‐functional bionic demonstrates that the vascular stent can achieve good anti‐thrombosis and in‐stent restenosis effects, which indicates its potential values in vascular intervention and other biomedical fields.
Effect of a Community Health Worker Intervention on Acute Care Use, Advance Care Planning, and Patient-Reported Outcomes Among Adults With Advanced Stages of Cancer
Authors: Manali I. Patel, Kristopher Kapphahn, Marilyn Dewland, Veronica Aguilar, Blanca Sanchez, Etsegenet Sisay, Ariana Murillo, Kim Smith, David J. Park
Journal: JAMA Oncology (2022)

<h3>Importance</h3> Deficiencies in advance care planning and symptom management are associated with avoidable acute care use among patients with cancer. Community health worker (CHW)–led approaches may be an approach to reduce acute care use but remain untested in community settings. <h3>Objective</h3> To determine whether a CHW-led advance care planning and symptom screening intervention can reduce acute care use more than usual care in a community setting. <h3>Design, Setting, and Participants</h3> This randomized clinical trial was conducted among patients with newly diagnosed advanced-stage or recurrent solid and hematologic cancers from August 8, 2017, through November 30, 2021. Data analysis was performed November 30, 2021, through January 1, 2022, by intention to treat. <h3>Interventions</h3> Participants were randomized 1:1 to usual care (control group) or usual care with the 6-month CHW-led intervention (intervention group). <h3>Main Outcomes and Measures</h3> The primary outcome was acute care use. Secondary outcomes included advance care planning documentation, supportive care use, patient-reported outcomes, survival, and end-of-life care use. <h3>Results</h3> Among 128 participants, median (range) age was 67 (19-89) years; 61 (47.7%) were female; and 2 (1.6%) were American Indian or Alaska Native, 11 (8.6%) were Asian, 5 (3.9%) were Black, 23 (18.0%) were Hispanic or Latino, 2 (1.6%) were of mixed race, 2 (1.6%) were Native Hawaiian or other Pacific Islander, 86 (67.2%) were White, and 20 (15.6%) did not report race. Intervention participants had 62% lower risk of acute care use than the control (hazard ratio, 0.38; 95% CI, 0.19-0.76) within 6 months. At 12 months, intervention participants had 17% lower odds of acute care use (odds ratio [OR], 0.83; 95% CI, 0.69-0.98), 8 times the odds of advance care planning documentation (OR, 7.18; 95% CI, 2.85-18.13), 4 times the odds of palliative care (OR, 4.46; 95% CI, 1.88-10.55), nearly double the odds of hospice (OR, 1.83; 95% CI, 1.16-2.88), and nearly double the odds of improved mental and emotional health from enrollment to 6 and 12 months postenrollment (OR, 1.82; 95% CI, 1.03-3.28; and OR, 2.20; 95% CI, 1.04-4.65, respectively) than the control. There were no differences in the death (control, 26 [40.6%] vs intervention, 32 [50.0%]). Fewer intervention participants had acute care use (0 vs 6 [23.1%]) in the month before death than the control. <h3>Conclusions and Relevance</h3> In this randomized clinical trial, integration of a CHW-led intervention into cancer care reduced acute care use and is one approach to improve cancer care delivery for patients with advanced stages of disease in community settings. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03154190
Challenges in the management of inflammatory bowel disease in sub-Saharan Africa
Authors: Gillian Watermeyer, Yaw Awuku, Ernst Fredericks, David Epstein, Mashiko Setshedi, Smita Devani, Wisdom Mudombi, Chris Kassianides, Leolin Katsidzira
Journal: The Lancet. Gastroenterology & hepatology (2022)
Breast Masses in Biological Females
Authors: Monique Swain, Myrlene Jeudy
Journal: JAMA (2022)

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